Association of the KCNJ11 variant E23K with type 2 diabetes in indo-trinidadians

Objective: To examine the effect of genetic variation in KCNJ11 on the risk of Type 2 diabetes mellitus in Trinidadians. Methods: The coding and bordering intron-exon regions of the KCNJ11 gene were sequenced in 168 diabetic and 61 non-diabetic subjects who historically were thought to be of South Asian Indian ancestry, as well as 66 diabetic and 59 non-diabetic subjects of African ancestry. Allele and haplotype frequency differences were calculated between cases and controls and linkage equilibrium was assessed across the KCNJ11 region. Results: We identified novel missense mutations in both subject groups including A94P and R369C in a diabetic Indo-Trinidadian subject, S113G in a non-diabetic Indo-Trinidadian subject, and S118L in a diabetic Afro-Trinidadian subject. It is unknown if these mutations are pathogenic as other family members were not available for study. Additionally, the common variant E23K was associated with Type 2 diabetes in the Indo-Trinidadian group (OR = 1.797 [1.148-2.814], p = 0.0098). Conclusions: Rare variants in KCNJ11 are segregating in the Indo- and Afro-Trinidadian populations and further studies are needed to determine their contribution, if any, to the overall prevalence of diabetes in these groups. Common variants such as E23K may increase the risk in the Indo-Trinidadian population.